Overexpression of mouse Mdm2 induces developmental phenotypes in Drosophila
Overexpression of mouse Mdm2 induces developmental phenotypes in Drosophila
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DOI：
10.1038/sj.onc.1205305
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发表时间：
2002-04-04
期刊：
影响因子：
8
通讯作者：
Oren, M
中科院分区：
文献类型：
--
作者：
Folberg-Blum, A;Sapir, A;Oren, M
Mdm2 原癌基因在多种肿瘤中扩增并过度表达。迄今为止，Mdm2 的主要功能之一是其调节肿瘤抑制蛋白 p53 的水平和活性的能力。 Mdm2 与 p53 的 N 末端结合，并通过其作为 E3 泛素连接酶的作用，靶向 p53 进行快速蛋白酶体降解。 Mdm2 还可以结合其他细胞蛋白，例如 hNumb、E2F1、Rb 和 Akt；然而，这些相互作用的生物学意义尚不清楚。为了深入了解 Mdm2 在体内的功能，我们生成了带有小鼠 Mdm2 基因的转基因果蝇菌株。使用 UAS/GAL4 系统的 Mdm2 异位表达会导致果蝇出现眼睛和翅膀表型。对三龄幼虫翅成虫盘的分析表明，Mdm2 的表达会诱导细胞凋亡。杂交并未揭示 Mdm2 与 E2F、Numb 和 Akt 的果蝇同源物之间的遗传相互作用。这些转基因果蝇可能为探索 Mdm2 在发育背景下的分子相互作用提供独特的实验模型。
The Mdm2 proto-oncogene is amplified and overexpressed in a variety of tumors. One of the major functions of Mdm2 described to date is its ability to modulate the levels and activity of the tumor suppressor protein p53. Mdm2 binds to the N-terminus of p53 and, through its action as an E3 ubiquitin ligase, targets p53 for rapid proteasomal degradation. Mdm2 can also bind to other cellular proteins such as hNumb, E2F1, Rb and Akt; however, the biological significance of these interactions is less clear. To gain insight into the function of Mdm2 in vivo, we have generated a transgenic Drosophila strain bearing the mouse Mdm2 gene. Ectopic expression of Mdm2, using the UAS/GAL4 system, causes eye and wing phenotypes in the fly. Analysis of wing imaginal discs from third instar larvae showed that expression of Mdm2 induces apoptosis. Crosses did not reveal genetic interactions between Mdm2 and the Drosophila homolog of E2F, Numb and Akt. These transgenic flies may provide a unique experimental model for exploring the molecular interactions of Mdm2 in a developmental context.